Clinical and Experimental Medicine

, Volume 19, Issue 3, pp 289–298 | Cite as

Adeno-associated virus as a gene therapy vector: strategies to neutralize the neutralizing antibodies

  • Majid Lotfinia
  • Meghdad Abdollahpour-Alitappeh
  • Behzad Hatami
  • Mohammad Reza Zali
  • Morteza KarimipoorEmail author
Review Article


Adeno-associated virus (AAV)-derived vectors are currently the most common type of viral vectors used in gene therapy clinical trials. The presence of neutralizing antibodies (NAbs) against wild-type AAVs in the host body is one of the limitations for the successful use of AAV vectors. AAV capsid manipulation, by which recombinant vectors lose their ability to interact with NAbs, can help overcome this obstacle. Various methods can be used for this purpose, including directed evolution as well as conjugation of certain chemical groups to AAV epitopes. The present review concisely explains the use of AAV vectors in the clinic for gene therapy of some diseases, their limitations, and solutions to these limitations.


Gene therapy Adeno-associated vectors Neutralizing antibodies Capsid modification 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval statement

We confirm that the manuscript has not been submitted or previously published in whole or in part elsewhere and is not split up into several parts to increase the quantity of submissions (“salami-publishing”). The manuscript is not currently being considered for publication in another journal. In addition, no data have been fabricated or manipulated (including images) to support our conclusions and no data, text, or theories by others are presented as if they were the author’s own (“plagiarism”). All authors, whose names appear on the submission, have been personally and actively involved in substantive work leading to the manuscript have, and all agreed to submit the manuscript to this journal.

Human and animal rights

The manuscript contains no studies with human participants or animals performed by any of the authors.

Informed consent

Formal consent is not required for this type of study.


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Molecular Medicine, Biotechnology Research CenterPasteur Institute of IranTehranIran
  2. 2.Physiology Research CenterKashan University of Medical SciencesKashanIran
  3. 3.Department of Nursing, School of NursingLarestan University of Medical SciencesLarestanIran
  4. 4.Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver DiseasesShahid Beheshti University of Medical SciencesTehranIran

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